Lead Investigator: Professor David Allsop
Institution: Lancaster University
Grant type: Project grant
Grant amount: £149,164
Start date: December 2014
Completion date: November 2016
Scientific Title: Biodistribution, pharmacokinetic and toxicity studies on a novel retro-inverso peptide inhibitor of beta-amyloid oligomer formation
What was the project, and what did the researchers do?
During Alzheimer’s disease, a protein called amyloid begins to clump together, until it forms large plaques that are deposited outside of brain cells. It is thought that the amyloid protein is toxic to nerve cells even when only a small number of pieces of protein have clumped together, before they have formed larger plaques.
Professor Allsop and his team have developed a chemical that binds to small pieces of amyloid, preventing them from clumping together. Unfortunately, the chemical is unable to cross the layer around the brain, called the blood-brain barrier, which prevents harmful things from entering the brain. In order to combat this problem and allow the chemical to enter the brain they linked the chemical to a special capsule called a nanoliposome. These nanoliposome capsules have previously been shown to be able to deliver different chemicals across the blood-brain barrier.
The team injected the chemical in the nanoliposome capsule into mice that have been genetically altered to show the symptoms of Alzheimer’s disease including amyloid plaques and memory loss. They investigated whether the drug helped to reduce the number of amyloid plaques, improve memory, and monitored for potential side-effects.
What were the key results, and how will this help in the fight against dementia?
The research team found that the drug is able to cross the blood brain barrier and enter the brain. Treatment of the mice with the drug reduced amyloid plaque numbers by 32% compared to a placebo treatment.
The team also worked with a research group in Italy that investigated the memory of the mice. They showed that treatment with this drug prevents the loss of memory in these mice.
These results are an encouraging step forward in the search for effective treatments to reduce or stop the development of amyloid clumps, which are thought to be one of the key causes of Alzheimer’s disease. Also, the use of nanoliposome capsules to deliver the drug across the blood-brain barrier is an exciting use of new techniques to develop drugs in the fight against Alzheimer’s disease.
What happened next? Future work and additional grants
The researchers in this study are now looking at moving this drug from mice models into clinical trials with people and have identified a Clinical Research Organisation that will design and run a clinical trial for the drug in the future.
How were people told about the results? Conferences and Publications
Gregori et al (2017) Retro-inverso peptide inhibitory nanoparticles as potent inhibitors of aggregation of the Alzheimer’s Aβ peptide. Nanomedicine: Nanotechnology, Biology and Medicine. Volume 13, Issue 2, Pages 723-732. doi: 10.1016/j.nano.2016.10.006
ARUK national meeting (Manchester) in March 2016.
Research highlighted on the Defying dementia website: http://www.lancaster.ac.uk/defyingdementia/